<scp>MIRO</scp>‐1 interacts with <scp>VDAC</scp>‐1 to regulate mitochondrial membrane potential in <i>Caenorhabditis elegans</i>

Ren, Xuecong; Zhou, Hengda; Sun, Yujie; Fu, Hongying; Ran, Yu; Yang, Bing; Yang, Fan; Björklund, Mikael; Xu, Suhong

doi:10.15252/embr.202256297

Cited by 4 publications

(1 citation statement)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Caenorhabditis elegans is a widely-used model organism for studying organelle dynamics and morphogenesis, including the nucleus, synaptic vesicles and mitochondria [19][20][21][22][23][24] . Disruption of intracellular transport of mitochondria is observed in unc-116, miro-1 and trak-1 mutant worms, where the molecular motor kinesin-1 and its adaptor proteins are mutated 20,21 . Orthologues of these proteins have similar functions in mammals and flies 24 .…”

Section: Introductionmentioning

confidence: 99%

SLC-25A46 Regulates Mitochondrial Fusion through FZO-1/Mitofusin and is Essential for Maintaining Neuronal Morphology

Obinata,

Takahashi,

Shimo

et al. 2024

Preprint

View full text Add to dashboard Cite

Mitochondria are dynamic organelles shaped by sequential fission and fusion events. The mitochondrial protein SLC25A46 has been identified as a causative gene for mitochondrial neuropathies. However, the function of SLC25A46 in mitochondrial morphogenesis remains controversial, with several reports suggesting it acts as a mitochondrial fission factor, while others propose it as a fusion factor. In this study, employing forward genetics, we identified slc-25A46, a Caenorhabditis elegans orthologue of human SLC25A46, as an essential factor for mitochondrial fusion. Suppressor mutagenesis screening revealed loss-of-function mutations in drp-1, a mitochondrial fission factor, as suppressors of slc-25A46. The phenotype of slc-25A46 mutants is similar to those of fzo-1 mutants, wherein the mitochondrial fusion factor Mitofusin is disrupted. Overexpressing FZO-1/Mitofusin mitigated mitochondrial defects in slc-25a46 mutants, indicating SLC-25A46 promotes fusion through FZO-1/Mitofusin. Disease model worms carrying mutations associated with SLC25A46 exhibited mitochondrial fragmentation and accelerated neurodegeneration, suggesting slc-25A46 maintains neuronal morphology through mitochondrial fusion regulation.

show abstract

Section: Introductionmentioning

confidence: 99%

SLC-25A46 Regulates Mitochondrial Fusion through FZO-1/Mitofusin and is Essential for Maintaining Neuronal Morphology

Obinata,

Takahashi,

Shimo

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Targeting VDAC: A potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease

Yang,

Jia,

Yang

et al. 2024

Brain Research

View full text Add to dashboard Cite

Reciprocal regulation of oxidative stress and mitochondrial fission augments parvalbumin downregulation through CDK5-DRP1- and GPx1-NF-κB signaling pathways

Wang,

Lee,

Kim

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

Loss of parvalbumin (PV) expressing neurons (PV neurons) is relevant to the underlying mechanisms of the pathogenesis of neurological and psychiatric diseases associated with the dysregulation of neuronal excitatory networks and brain metabolism. Although PV modulates mitochondrial morphology, volume and dynamics, it is largely unknown whether mitochondrial dynamics affect PV expression and what the molecular events are responsible for PV neuronal degeneration. In the present study, L-buthionine sulfoximine (BSO, an inhibitor of glutathione synthesis) did not degenerate PV neurons under physiological condition. However, BSO-induced oxidative stress decreased PV expression and facilitated cyclin-dependent kinase 5 (CDK5) tyrosine (Y) 15 phosphorylation, dynamin-related protein 1 (DRP1)-mediated mitochondrial fission and glutathione peroxidase-1 (GPx1) downregulation in PV neurons. Co-treatment of roscovitine (a CDK5 inhibitor) or mitochondrial division inhibitor-1 (Mdivi-1, an inhibitor of mitochondrial fission) attenuated BSO-induced PV downregulation. WY14643 (an inducer of mitochondrial fission) reduced PV expression without affecting CDK5 Y15 phosphorylation. Following status epilepticus (SE), CDK5 Y15 phosphorylation and mitochondrial fission were augmented in PV neurons. These were accompanied by reduced GPx1-mediated inhibition of NF-κB p65 serine (S) 536 phosphorylation. N-acetylcysteine (NAC), roscovitine and Mdivi-1 ameliorated SE-induced PV neuronal degeneration by mitigating CDK5 Y15 hyperphosphorylation, aberrant mitochondrial fragmentation and reduced GPx1-mediated NF-κB inhibition. Furthermore, SN50 (a NF-κB inhibitor) alleviated SE-induced PV neuronal degeneration, independent of dysregulation of mitochondrial fission, CDK5 hyperactivation and GPx1 downregulation. These findings provide an evidence that oxidative stress may activate CDK5-DRP1- and GPx1-NF-κB-mediated signaling pathways, which would be possible therapeutic targets for preservation of PV neurons in various diseases.

show abstract

MIRO‐1 interacts with VDAC‐1 to regulate mitochondrial membrane potential in Caenorhabditis elegans

Cited by 4 publications

References 46 publications

SLC-25A46 Regulates Mitochondrial Fusion through FZO-1/Mitofusin and is Essential for Maintaining Neuronal Morphology

SLC-25A46 Regulates Mitochondrial Fusion through FZO-1/Mitofusin and is Essential for Maintaining Neuronal Morphology

Targeting VDAC: A potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease

Reciprocal regulation of oxidative stress and mitochondrial fission augments parvalbumin downregulation through CDK5-DRP1- and GPx1-NF-κB signaling pathways

Contact Info

Product

Resources

About